TTFields + Pembrolizumab + Chemotherapy for Lung Cancer

(LUNAR-2 Trial)

Recruiting at 80 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: NovoCure GmbH

Must not be taking: Antineoplastics, Immunosuppressants

Disqualifiers: Mixed histology, EGFR mutation, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

734 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This study, known as LUNAR-2, aims to investigate the effectiveness and safety of using TTFields, delivered by the NovoTTF-200T device, concomitantly administered with pembrolizumab and platinum-based chemotherapy for patients with advanced non-small cell lung cancer that has spread to other parts of the body. The primary goals of the study are to assess overall survival and progression-free survival. Secondary objectives include analyzing outcomes based on the specific histology (subtype) of the lung cancer.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are expected to need other cancer treatments while in the study or if you are on certain immunosuppressive therapies.

Is the combination of TTFields, Pembrolizumab, and Chemotherapy safe for humans?

Pembrolizumab, a part of this treatment, has been used safely in humans for various cancers, but it can cause side effects like fatigue, cough, and nausea. Serious side effects, such as pneumonitis (lung inflammation), have been reported in a small percentage of patients. Always discuss potential risks with your doctor. ^{1 2 3 4 5}

What makes the TTFields + Pembrolizumab + Chemotherapy treatment unique for lung cancer?

This treatment is unique because it combines Tumor Treating Fields (TTFields), a non-invasive therapy that uses electric fields to disrupt cancer cell division, with pembrolizumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells, and platinum-based chemotherapy, which kills cancer cells directly. This combination aims to enhance the effectiveness of each component, potentially leading to better outcomes than using these treatments separately. ^{3 6 7 8 9}

What data supports the effectiveness of the treatment TTFields + Pembrolizumab + Chemotherapy for Lung Cancer?

Research shows that pembrolizumab, when combined with chemotherapy, improves survival in patients with advanced non-small cell lung cancer compared to chemotherapy alone. Additionally, pembrolizumab is effective as a first-line treatment for patients with high PD-L1 expression, enhancing overall survival and progression-free survival. ^{1 4 6 10 11}

Are You a Good Fit for This Trial?

This trial is for adults with advanced non-small cell lung cancer that has spread, who are in good physical condition (able to perform daily activities without significant limitations) and have not had previous systemic treatment for their metastatic disease. Women must not be pregnant or breastfeeding, and men must agree to use contraception.

Inclusion Criteria

I am fully active or can carry out light work.

I am 22 years old or older.

I am not pregnant or breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TTFields using the NovoTTF-200T device, pembrolizumab, and platinum-based chemotherapy

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 6 years

What Are the Treatments Tested in This Trial?

Interventions

• NovoTTF-200T
• Pembrolizumab
• Platinum-based Chemotherapy

Trial Overview The LUNAR-2 study tests the combination of TTFields delivered by NovoTTF-200T device with pembrolizumab and platinum-based chemotherapy. It aims to see if this mix can improve survival times for patients compared to current treatments, focusing on different subtypes of lung cancer.

How Is the Trial Designed?

Group I: Arm 1: NovoTTF-200T, Pembrolizumab, and Platinum-based Chemotherapy Experimental Treatment 3 Interventions

Subjects in this arm receive three treatments - TTFields using the NovoTTF-200T device, pembrolizumab, and platinum-based chemotherapy.

Group II: Arm 2: Pembrolizumab and Platinum-based Chemotherapy Active Control 2 Interventions

Subjects in this arm receive two treatments - pembrolizumab and platinum-based chemotherapy.

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

NovoCure GmbH

Lead Sponsor

Trials

16

Recruited

3,700+

Published Research Related to This Trial

In a real-life study of 121 patients with advanced non-squamous non-small cell lung cancer, the combination of pembrolizumab and chemotherapy resulted in a median progression-free survival of 9 months and overall survival of 20.6 months, demonstrating its efficacy as a first-line treatment.

The treatment was generally well-tolerated, with manageable side effects; however, 17.5% of patients experienced grade 3-4 adverse events, and there were two treatment-related deaths, indicating the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). Renaud, E., Ricordel, C., Corre, R., et al.[2023]

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

In a study of 187 patients with non-small-cell lung cancer (NSCLC) and PD-L1 expression of ≥50%, those with PD-L1 levels of 90%-100% showed significantly better treatment outcomes with pembrolizumab, including a higher overall response rate (60% vs. 32.7%) and longer median progression-free survival (14.5 months vs. 4.1 months).

Patients with higher PD-L1 expression not only had improved response rates but also longer overall survival, indicating that PD-L1 levels can be a critical factor in predicting the efficacy of pembrolizumab as a first-line treatment for NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes to first-line pembrolizumab in patients with non-small-cell lung cancer and very high PD-L1 expression. Aguilar, EJ., Ricciuti, B., Gainor, JF., et al.[2023]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

In a pooled analysis of 444 patients with PD-L1-negative advanced/metastatic non-small cell lung cancer (NSCLC), pembrolizumab combined with chemotherapy significantly improved overall survival (hazard ratio 0.63) and progression-free survival (hazard ratio 0.68) compared to chemotherapy alone.

Despite high rates of adverse events (99.2% in the pembrolizumab group), the combination therapy was manageable and resulted in an impressive objective response rate of 87.5% and a 3-year overall survival rate of 100% for patients completing 2 years of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus chemotherapy versus chemotherapy alone in patients with advanced non-small cell lung cancer without tumor PD-L1 expression: A pooled analysis of 3 randomized controlled trials. Borghaei, H., Langer, CJ., Paz-Ares, L., et al.[2021]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

In a phase 3 trial with 559 patients, the combination of pembrolizumab and chemotherapy significantly improved overall survival to 15.9 months compared to 11.3 months for chemotherapy alone, demonstrating a strong efficacy in treating metastatic squamous non-small-cell lung cancer (NSCLC).

The addition of pembrolizumab also resulted in a longer progression-free survival of 6.4 months versus 4.8 months for the placebo group, although there was a slightly higher rate of treatment discontinuation due to adverse events in the pembrolizumab group (13.3% vs. 6.4%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus Chemotherapy for Squamous Non-Small-Cell Lung Cancer. Paz-Ares, L., Luft, A., Vicente, D., et al.[2022]

In a review of five randomized trials with nearly 2,000 participants, both pembrolizumab (PEM) and tislelizumab (TIS) combined with chemotherapy showed significant improvements in progression-free survival (PFS) compared to chemotherapy alone, with median PFS of 8.89 months for PEM and 7.97 months for TIS.

The indirect comparison indicated that PEM and TIS have similar efficacy when combined with chemotherapy, meeting regulatory criteria for equivalence, suggesting that either treatment could be a viable option for patients with advanced non-small cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab plus chemotherapy vs. pembrolizumab plus chemotherapy for the first-line treatment of advanced non-small cell lung cancer: systematic review and indirect comparison of randomized trials. Messori, A., Rivano, M., Chiumente, M., et al.[2023]

In a phase 3 trial involving 616 patients with untreated metastatic nonsquamous non-small-cell lung cancer (NSCLC), the addition of pembrolizumab to standard chemotherapy significantly improved overall survival, with a 12-month survival rate of 69.2% compared to 49.4% for the placebo group.

Patients receiving pembrolizumab also experienced longer progression-free survival (8.8 months) compared to those on placebo (4.9 months), demonstrating the efficacy of pembrolizumab in enhancing treatment outcomes for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer. Gandhi, L., Rodríguez-Abreu, D., Gadgeel, S., et al.[2022]

Citations

1. China pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). [2023]

2. England pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Outcomes to first-line pembrolizumab in patients with non-small-cell lung cancer and very high PD-L1 expression. [2023]

4. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus chemotherapy versus chemotherapy alone in patients with advanced non-small cell lung cancer without tumor PD-L1 expression: A pooled analysis of 3 randomized controlled trials. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

8. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus Chemotherapy for Squamous Non-Small-Cell Lung Cancer. [2022]

10. China pubmed.ncbi.nlm.nih.gov

Tislelizumab plus chemotherapy vs. pembrolizumab plus chemotherapy for the first-line treatment of advanced non-small cell lung cancer: systematic review and indirect comparison of randomized trials. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer. [2022]